Systems, devices, and methods for ovarian denervation

ABSTRACT

Methods for effectuating ovarian denervation include advancing a disruptor intravaginally to access an ovarian nerve and applying the disruptor to the ovarian nerve to denervate the ovarian nerve to limit ovarian sympathetic neural activity and control hormonal secretion.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication No. 62/561,601, filed Sep. 21, 2017, the entire contents ofwhich are incorporated by reference herein.

TECHNICAL FIELD

The present disclosure relates to ovarian denervation and, moreparticularly, to systems, devices, and methods for disrupting ovariannerve supply to limit ovarian sympathetic neural activity and controlhormonal secretion.

BACKGROUND

Ovarian sympathetic neural activity can cause or exacerbate severalovarian conditions, including common endocrine disorders affecting womenof reproductive ages (e.g., 12-45 years old) such as Polycystic OvarySyndrome (PCOS) and Premenstrual Dysphoric Disorder (PMDD). Scientificliterature suggests that ovarian hormonal secretion is regulated bysympathetic nervous activity to the ovary. The sympathetic nervoussystem (SNS) is a primarily involuntary bodily control system typicallyassociated with stress responses. Fibers of the SNS extend throughtissue in almost every organ system of the human body. For example, somefibers extend from the brain, intertwine along the aorta, and branch outto various organs. As groups of fibers approach specific organs, fibersparticular to the organs can separate from the groups. Signals sent viathese and other fibers can affect characteristics such as pupildiameter, gut motility, and urinary output. Such regulation can haveadaptive utility in maintaining homeostasis or in preparing the body forrapid response to environmental factors. Chronic activation of the SNS,however, is a common maladaptive response that can drive the progressionof many disease states. Excessive activation of the ovarian SNS has beenidentified experimentally and in humans as a likely contributor to thecomplex pathophysiology of PCOS.

SUMMARY

In accordance with an aspect of the present disclosure, a method foreffectuating ovarian denervation includes advancing a disruptorintravaginally and through a vaginal fornix to access a positionadjacent an ovarian nerve. The method includes activating the disruptorto denervate the ovarian nerve.

The disruptor may include an ablation device, and advancing thedisruptor through the vaginal fornix may include advancing the ablationdevice through the vaginal fornix. Activating the disruptor may includeablating the ovarian nerve with the ablation device.

In certain aspects of the present disclosure, the method may furtherinclude advancing an ultrasound probe intravaginally and positioning theultrasound probe to enable the ultrasound probe to project ultrasound inalignment with an ovary while the disrupter is activated. The disruptermay be coupled to the ultrasound probe, and the disruptor and theultrasound probe may be introduced intravaginally together. The methodmay further include advancing the disruptor relative to the ultrasoundprobe. A guide tube may be coupled to the ultrasound probe; andadvancing the disruptor relative to the ultrasound probe may includeadvancing the disruptor through the guide tube. Advancing the disruptorthrough the guide tube may include directing the disruptor away from theultrasound probe as the disruptor is advanced relative to the ultrasoundprobe. Directing the disruptor away from the ultrasound probe mayinclude intravaginally positioning the guide tube such that the guidetube directs the disruptor toward the vaginal fornix.

In some aspects of the present disclosure, activating the disruptor maydisrupt a myelin sheath of the ovarian nerve without disrupting a nervefiber of the ovarian nerve.

In certain aspects of the present disclosure, activating the disruptormay include applying microwave energy to the ovarian nerve.

In aspects of the present disclosure, activating the disruptor mayinclude applying electrosurgical plasma to the ovarian nerve.

In some aspects of the present disclosure, activating the disruptor mayinclude applying a blade to the ovarian nerve.

According to yet another aspect of the present disclosure, an ovariandenervation system is provided. The ovarian denervation system includesan intravaginal ultrasound probe, a guide tube coupled to theintravaginal ultrasound probe, and a disruptor. The disruptor isadvanceable through the guide tube and relative to the intravaginalultrasound probe. The disruptor is configured to advance through avaginal fornix to access a position adjacent an ovarian nerve. Thedisruptor is configured to denervate the ovarian nerve.

In some embodiments of the present disclosure, the disruptor may includean end effector that is configured to ablate the ovarian nerve withmicrowave energy.

In certain embodiments of the present disclosure, the disruptor mayinclude an end effector that is configured to emit electrosurgicalplasma for disrupting the ovarian nerve.

In embodiments of the present disclosure, the disruptor may include ablade that may be configured to scrape the ovarian nerve.

In some embodiments of the present disclosure, the guide tube includes acurved distal portion configured to direct the disruptor toward thevaginal fornix.

In certain embodiments, the disruptor may be configured to disrupt amyelin sheath of a first ovarian nerve without disrupting a nerve fiberof the first ovarian nerve.

According to still another aspect of the present disclosure, a methodfor effectuating ovarian denervation includes advancing a disruptorintravaginally and through a fundus of a uterus to a position adjacentan ovarian nerve, and activating the disruptor to denervate the ovariannerve.

In aspects of the present disclosure, the disruptor may include anablation device, and advancing the disruptor through the fundus includesadvancing the ablation device through the fundus.

In some aspects of the present disclosure, the method includes advancingan ultrasound probe intravaginally and positioning the ultrasound probeto project ultrasound in alignment with an ovary while the disrupter isactivated. The disrupter may be coupled to the ultrasound probe, and thedisruptor and the ultrasound probe may be introduced intravaginallytogether. The method may further include advancing the disruptorrelative to the ultrasound probe. A guide tube may be coupled to theultrasound probe; and advancing the disruptor relative to the ultrasoundprobe may include advancing the disruptor through the guide tube.Advancing the disruptor through the guide tube may include directing thedisruptor away from the ultrasound probe as the disruptor is advancedrelative to the ultrasound probe. Directing the disruptor away from theultrasound probe may include intravaginally positioning the guide tubesuch that the guide tube directs the disruptor toward the fundus.

According to yet another aspect of the present disclosure, an ovariandenervation system includes an intravaginal ultrasound probe, a guidetube coupled to the intravaginal ultrasound probe, and a disruptor. Thedisruptor is advanceable through the guide tube and relative to theintravaginal ultrasound probe. The disruptor is configured to advancethrough a a fundus of a uterus to a position adjacent an ovarian nerve.The disruptor is configured to denervate the ovarian nerve.

In some embodiments of the present disclosure, the guide tube mayinclude a curved distal portion configured to direct the disruptortoward the fundus.

According to still another aspect of the present disclosure, a methodfor effectuating ovarian denervation includes advancing a disruptorintravaginally and into a fallopian tube to access an ovarian nerve, andactivating the disruptor to denervate the ovarian nerve.

In some aspects of the present disclosure, the disruptor may include anablation device, and advancing the disruptor through the fallopian tubemay include advancing the ablation device through the fallopian tube.

In certain aspects of the present disclosure, the method may furtherinclude advancing the disruptor to a position adjacent to aninfundibulopelvic ligament.

In aspects of the present disclosure, the method may further includeadvancing an ultrasound probe intravaginally, and positioning theultrasound probe to project ultrasound in alignment with an ovary whilethe disrupter is activated. The method may further include advancing thedisruptor relative to the ultrasound probe. A guide tube may be coupledto the ultrasound probe, and advancing the disruptor relative to theultrasound probe may include advancing the disruptor through the guidetube. Advancing the disruptor through the guide tube may includedirecting the disruptor away from the ultrasound probe as the disruptoris advanced relative to the ultrasound probe. Directing the disruptoraway from the ultrasound probe may include intravaginally positioningthe guide tube such that the guide tube directs the disruptor toward theuterus.

According to yet another aspect of the present disclosure, an ovariandenervation system includes an intravaginal ultrasound probe, a guidetube coupled to the intravaginal ultrasound probe, and a disruptor. Thedisruptor is advanceable through the guide tube and relative to theintravaginal ultrasound probe. The disruptor is configured to advanceinto a fallopian tube to a position adjacent an ovarian nerve. Thedisruptor is configured to denervate the ovarian nerve.

In some embodiments, the guide tube includes a curved distal portionconfigured to direct the disruptor toward the fallopian tube.

According to still another aspect of the present disclosure, a methodfor effectuating ovarian denervation includes introducing a catheterinto an ovarian vessel, and expanding a balloon within the ovarianvessel to disrupt an ovarian nerve that extends along the ovarian vesselwithout tearing a wall of the ovarian vessel.

The method may further include positioning the balloon adjacent aninfundibulopelvic ligament that supports the ovarian vessel.

In some aspects of the present disclosure, expanding the balloon mayinclude inflating the balloon with inflation fluid.

In certain aspects of the present disclosure, the method may includedeflating the balloon and positioning the balloon within a secondovarian vessel for re-inflation. The method may further includere-inflating the balloon within the second ovarian vessel to disrupt asecond ovarian nerve that extends along the second ovarian vesselwithout tearing a wall of the second ovarian vessel.

In some aspects of the present disclosure, expanding the balloon mayinclude tearing the ovarian nerve that extends along the ovarian vesselwithout tearing the wall of the ovarian vessel.

According to still another aspect of the present disclosure, a methodfor effectuating ovarian denervation includes implanting one or moreelectrodes within an ovarian vessel, and activating the one or moreelectrodes to disrupt an ovarian nerve.

In some aspects of the present disclosure, the method may furtherinclude implanting one or more additional electrodes adjacent to theovarian vessel. The method may include activating the one or moreadditional electrodes to disrupt an ovarian nerve. Activating the one ormore additional electrodes may include intermittently conductingelectrical energy through the one or more additional electrodes.Implanting the one or more additional electrodes may include implantingthe one or more additional electrodes adjacent to an infundibulopelvicligament.

In certain aspects, implanting the one or more electrodes may includeimplanting the one or more electrodes within an infundibulopelvicligament. Activating the one or more electrodes may includeintermittently conducting electrical energy through the one or moreelectrodes.

According to yet another aspect of the present disclosure, a method foreffectuating ovarian denervation includes implanting one or moreelectrodes adjacent to an ovarian vessel, and activating the one or moreelectrodes to disrupt an ovarian nerve.

In some aspects of the present disclosure, implanting the one or moreelectrodes includes implanting the one or more electrodes adjacent to aninfundibulopelvic ligament.

Other aspects, features, and advantages will be apparent from thedescription, the drawings, and the claims that follow.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate embodiments of the presentsystems, devices, and methods for disrupting an ovarian nerve and,together with a general description of the disclosure given above, andthe detailed description given below, serve to explain the principles ofthe disclosure, wherein:

FIGS. 1A and 1B are anatomical views illustrating vaginal tissue.

FIG. 1C is an anatomical view illustrating an ovarian artery and nearbyorgans and vessels.

FIG. 1D is a partial, cross-sectional view illustrating an ovariandenervation technique in accordance with one aspect of the presentdisclosure.

FIG. 2 is a conceptual illustration of a sympathetic nervous system(SNS) and how a brain communicates with a body via the SNS.

FIG. 3 is an enlarged anatomic view of arterial vasculature anatomy ofan ovary.

FIG. 4 is a side view of an ovarian denervation system in accordancewith an illustrative embodiment of the present disclosure.

FIG. 5A is an anatomical view of vaginal tissue including illustrationsof projected trajectories of components of the ovarian denervationsystem of FIG. 4 in accordance with an aspect of an ovarian denervationtechnique of the present disclosure.

FIG. 5B is a schematic view illustrating an aspect of the ovariandenervation technique of FIG. 5A.

FIGS. 6-10 are views illustrating different ovarian denervationtechniques in accordance with various aspects of the present disclosure.

FIGS. 11A and 11B are progressive views illustrating an ovariandenervation technique involving a balloon catheter in accordance with anaspect of the present disclosure.

FIG. 12A-12B are anatomical views of nerve fiber and its myelin sheathin a normal state.

FIG. 12C is an anatomical view of the nerve fiber and its myelin sheathin a disrupted state.

DETAILED DESCRIPTION

A need exists to provide systems, devices, and/or methods for disruptingnerve supply to an ovary.

Although the presently disclosed systems, devices, methods are describedherein with respect to ovarian denervation, these systems, devices,and/or methods may be modified for disrupting the nerve supply to otherorgans or body systems or to treat other diseases or conditions.

Embodiments of the presently disclosed systems, devices, and/or methodsfor disrupting ovarian nerve supply are described in detail withreference to the drawings, in which like reference numerals designateidentical or corresponding elements in each of the several views. Asused herein, the term “distal” refers to that portion of structurefarther from the user, while the term “proximal” refers to that portionof structure, closer to the user. As used herein, the term “clinician”refers to a doctor, nurse, or other care provider and may includesupport personnel. As used herein, the terms “denervation,” “disruption”or other similar terms refer to any loss in, or damage to, nerve supplyincluding partial or complete loss of, or damage to, nerve supply.

In the following description, well-known functions or constructions arenot described in detail to avoid obscuring the present disclosure inunnecessary detail.

The vaginal anatomy is generally illustrated in FIGS. 1A-1D. FIG. 1C, inparticular, is an anatomical view illustrating the ovaries 10 and nearbyorgans and vessels, including an ovarian artery 12. Treatment proceduresfor ovarian denervations or disruptions, in accordance with embodimentsof the present technology, can include applying a treatment modality atone or more treatment locations proximate a structure having arelatively high concentration of ovarian nerves. In some aspects, forexample, at least one treatment location can be proximate a portion ofthe ovarian artery 12, a branch of the ovarian artery 12, an ostium ofthe ovarian artery 12, an ovarian vein 14, a branch of an ovarian vein,an ostium of an ovarian vein, and/or another suitable structure (e.g.,another suitable structure extending along the suspensory ligament) inthe vicinity of ovarian nerves.

FIG. 1D is a cross-sectional view illustrating denervation at atreatment location within the ovarian artery 12. As shown in FIG. 1D, atreatment device 16 including a shaft 18 and an end effector 20supported thereon, can be extended toward the ovarian artery 12 tolocate the end effector 20 at the treatment location within the ovarianartery 12. The end effector 20 can be configured for denervation at thetreatment location via a suitable treatment modality, e.g., direct heat,electrode-based, microwave, light, ultrasonic, or another suitabletreatment modality.

With continued reference to FIGS. 1A-1D, the treatment location can beproximate (e.g., at or near) a vessel or chamber wall (e.g., a wall ofan ovarian artery, an ovarian vein, and/or another suitable structure),and the treated tissue can include tissue proximate the treatmentlocation. For example, with regard to the ovarian artery 12, a treatmentprocedure can include ablating nerves in the ovarian plexus, which layat least partially within or adjacent to the adventitia of the ovarianartery. In some embodiments, it may be desirable to disrupt ovariannerves from a treatment location within a tubular structure or vesseland in close proximity to an ovary, e.g., closer to the ovary 10 than toa trunk of the vessel. This can increase the likelihood of disruptingnerves specific to the ovary, while decreasing the likelihood ofdisrupting nerves that extend to other organs. Vessels can decrease indiameter and become more tortuous as they extend toward an ovary 10.Accordingly, disrupting ovarian nerves from a treatment location inclose proximity to an ovary can include using a device (e.g., treatmentdevice 16) having size, flexibility, torque-ability, kink resistance,and/or other characteristics suitable for accessing narrow and/ortortuous portions of vessels.

Energy delivery techniques, such as an electrode-based approach, forexample, can be used for ovarian denervation. Electrode-based treatmentcan include delivering electrical energy and/or another form of energyto tissue and/or heating tissue at a treatment location in a manner thatdisrupts neural function. For example, sufficiently disrupting at leasta portion of a sympathetic ovarian nerve can slow or potentially blockconduction of neural signals to produce a prolonged or permanentreduction in sympathetic activity. Some suitable energy modalities caninclude, for example, RF energy (monopolar and/or bipolar), pulsed RFenergy, microwave energy, ultrasound energy (e.g., intravascularlydelivered ultrasound, extracorporeal ultrasound, HIFU), laser energy,optical energy, magnetic energy, direct heat, or other suitable energymodalities alone or in combination. Where a system uses a monopolarconfiguration, a return electrode or ground patch fixed externally onthe subject can be used. Moreover, electrodes (or other energy deliveryelements) can be used alone or with other electrodes in amulti-electrode array. Examples of suitable multi-electrode devices aredescribed in U.S. Patent Application Publication No. 2012/0116382, andincorporated herein by reference in its entirety. Other suitable devicesand technologies, such as thermal devices, are described in U.S. PatentApplication Publication No. 2012/0136350, also incorporated herein byreference in its entirety.

Thermal effects can include both thermal ablation and non-ablativethermal alteration or damage (e.g., via sustained heating and/orresistive heating) to partially or completely disrupt the ability of anerve to transmit a signal. Desired thermal heating effects, forexample, may include raising the temperature of target neural fibersabove a desired threshold to achieve non-ablative thermal alteration, orabove a higher temperature to achieve ablative thermal alteration. Forexample, the target temperature can be above body temperature (e.g.,approximately 37° C.), but less than about 45° C. for non-ablativethermal alteration, or the target temperature can be about 45° C. orhigher kw ablative thermal alteration. More specifically, exposure tothermal energy in excess of a body temperature of about 37° C., butbelow a temperature of about 45° C., may induce thermal alteration viamoderate heating of target neural fibers or of vascular structures thatperfuse the target fibers. In cases where vascular structures areaffected, the target neural fibers may be denied perfusion resulting innecrosis of the neural tissue. For instance, this may inducenon-ablative thermal alteration in the fibers or structures. Exposure toheat above a temperature of about 45° C., or above about 60° C., mayinduce thermal alteration via substantial heating of the fibers orstructures. For example, such higher temperatures may thermally ablatethe target neural fibers or the vascular structures that perfuse thetarget fibers. In some patients, it may be desirable to achievetemperatures that thermally ablate the target neural fibers or thevascular structures, but that are less than about 90° C., or less thanabout 85° C., or less than about 80° C., and/or less than about 75° C.Other aspects can include heating tissue to a variety of other suitabletemperatures.

In some aspects of the present disclosure, a treatment procedure caninclude applying a suitable treatment modality at a treatment locationin a testing step followed by a treatment step. The testing step, forexample, can include applying the treatment modality at a lowerintensity and/or fix a shorter duration than during the treatment step.This can allow an operator to determine (e.g., by neural activitysensors and/or patient feedback) whether nerves proximate the treatmentlocation are suitable for denervation. Performing a testing step can beparticularly useful for treatment procedures in which targeted nervesare closely associated with nerves that could cause undesirable sideeffects if disrupted during a subsequent treatment step.

In accordance with the present technology, denervation of a left and/orright ovarian nerve (e.g., ovarian plexus), which is intimatelyassociated with a left and/or right ovarian artery 12 (FIG. 1C), may beachieved through intravascular access.

The following discussion provides further details regarding pertinentpatient anatomy and physiology. This section is intended to supplementand expand upon the previous discussion regarding the relevant anatomyand physiology, and to provide additional context regarding thedisclosed technology and the benefits associated with ovariandenervation.

With reference to FIG. 2, the sympathetic nervous system (SNS) is abranch of the autonomic nervous system along with the enteric nervoussystem and parasympathetic nervous system. It is always active at abasal level (called sympathetic tone) and becomes more active duringtimes of stress. Like other parts of the nervous system, the SNSoperates through a series of interconnected neurons. Sympathetic neuronsare frequently considered part of the peripheral nervous system (PNS),although many lie within the central nervous system (CNS). Sympatheticneurons of the spinal cord (which is part of the CNS) communicate withperipheral sympathetic neurons via a series of sympathetic ganglia.Within the ganglia, spinal cord sympathetic neurons join peripheralsympathetic neurons through synapses. Spinal cord sympathetic neuronsare therefore called presynaptic (or preganglionic) neurons, whileperipheral sympathetic neurons are called postsynaptic (orpostganglionic) neurons.

At synapses within the sympathetic ganglia, preganglionic sympatheticneurons release acetylcholine, a chemical messenger that binds andactivates nicotinic acetylcholine receptors on postganglionic neurons.In response to this stimulus, postganglionic neurons principally releasenoradrenaline (norepinephrine). Prolonged activation may elicit therelease of adrenaline from the adrenal medulla.

Once released, norepinephrine binds adrenergic receptors on peripheraltissues. Binding to adrenergic receptors causes a neuronal and hormonalresponse. The physiologic manifestations include pupil dilation,increased heart rate, occasional vomiting, and increased blood pressure.Increased sweating is also seen due to binding of cholinergic receptorsof the sweat glands.

The SNS is responsible for up- and down-regulation of many homeostaticmechanisms in living organisms. Fibers from the SNS innervate tissues inalmost every organ system, providing at least some regulatory functionto physiological features as diverse as pupil diameter, gut motility,and urinary output. This response is also known as the sympatho-adrenalresponse of the body, as the preganglionic sympathetic fibers that endin the adrenal medulla (but also all other sympathetic fibers) secreteacetylcholine, which activates the secretion of adrenaline (epinephrine)and to a lesser extent noradrenaline (norepinephrine). Therefore, thisresponse that acts primarily on the cardiovascular system is mediateddirectly via impulses transmitted through the SNS and indirectly viacatecholamines secreted from the adrenal medulla.

Science typically looks at the SNS as an automatic regulation system,that is, one that operates without the intervention of consciousthought. Some evolutionary theorists suggest that the SNS operated inearly organisms to maintain survival as the SNS is responsible forpriming the body for action. One example of this priming is in themoments before waking, in which sympathetic outflow spontaneouslyincreases in preparation for action.

The Sympathetic Chain

As shown in FIG. 2, the SNS provides a network of nerves that allows thebrain to communicate with the body. Sympathetic nerves originate insidethe vertebral column, toward the middle of the spinal cord in theintermediolateral cell column (or lateral horn), beginning at the firstthoracic segment of the spinal cord and are thought to extend to thesecond or third lumbar segments. Because its cells begin in the thoracicand lumbar regions of the spinal cord, the SNS is said to have athoracolumbar outflow. Axons of these nerves leave the spinal cordthrough the anterior rootlet/root. They pass near the spinal (sensory)ganglion, where they enter the anterior rami of the spinal nerves.However, unlike somatic innervation, they quickly separate out throughwhite rami connectors that connect to either the paravertebral (whichlie near the vertebral column) or prevertebral (which lie near theaortic bifurcation) ganglia extending alongside the spinal column.

In order to reach the target organs and glands, the axons travel longdistances in the body. Many axons relay their message to a second cellthrough synaptic transmission. The first cell (the presynaptic cell)sends a neurotransmitter across the synaptic cleft (the space betweenthe axon terminal of the first cell and the dendrite of the second cell)where it activates the second cell (the postsynaptic cell). The messageis then propagated to the final destination.

In the SNS and other neuronal networks of the peripheral nervous system,these synapses are located at sites called ganglia, discussed above. Thecell that sends its fiber to a ganglion is called a preganglionic cell,while the cell whose fiber leaves the ganglion is called apostganglionic cell. As mentioned previously, the preganglionic cells ofthe SNS are located between the first thoracic (T1) segment and thirdlumbar (L3) segments of the spinal cord. Postganglionic cells have theircell bodies in the ganglia and send their axons to target organs orglands. The ganglia include not just the sympathetic trunks but also thecervical ganglia (superior, middle and inferior), which sendssympathetic nerve fibers to the head and thorax organs, and the celiacand mesenteric ganglia (which send sympathetic fibers to the gut).

Innervation of the Ovaries

The ovaries and part of the fallopian tubes and broad ligament of theuterus are innervated by the ovarian plexus, a network of nerve fibersaccompanying the ovarian vessels and derived from the aortic and renalplexuses. As FIG. 3 shows, the blood supply to the ovary is provided bythe ovarian artery. The ovarian plexus is an autonomic plexus thatsurrounds the ovarian artery and is carried in the suspensory ligament.The ovarian plexus extends along the ovarian artery until it arrives atthe substance of the ovary. Fibers contributing to the ovarian plexusarise from the renal plexus, celiac ganglion, the superior mesentericganglion, the aorticorenal ganglion and the aortic plexus. The ovarianplexus, also referred to as the ovarian nerve, is predominantlycomprised of sympathetic nerve fibers.

Preganglionic neuronal cell bodies are located in the intermediolateralcell column of the spinal cord. Preganglionic axons pass through theparavertebral ganglia (they do not synapse) to become the lessersplanchnic nerve, the least splanchnic nerve, the first lumbarsplanchnic nerve, and the second lumbar splanchnic nerve, and theytravel to the celiac ganglion, the superior mesenteric ganglion, and theaorticorenal ganglion. Postganglionic neuronal cell bodies exit theceliac ganglion, the superior mesenteric ganglion, and the aorticorenalganglion to the renal plexus, which are distributed to the renalvasculature, and give rise to the ovarian plexus which is distributed tothe ovary and the fundus of the uterus.

Ovarian Sympathetic Neural Activity

Messages trawl through the SNS in a bidirectional flow. Efferentmessages may trigger changes in different parts of the bodysimultaneously. For example, the SNS may accelerate heart rate; widenbronchial passages; decrease motility (movement) of the large intestine;constrict blood vessels; increase peristalsis in the esophagus; causepupil dilation, cause piloerection (i.e., goose bumps), causeperspiration (i.e., sweating), and raise blood pressure. Afferentmessages carry signals from various organs and sensory receptors in thebody to other organs and, particularly, the brain.

Hypertension, heart failure and chronic kidney disease are a few of manydisease states that result from chronic activation of the SNS,especially the renal sympathetic nervous system. Chronic activation ofthe SNS is a maladaptive response that drives the progression of thesedisease states. Pharmaceutical management of therenin-angiotensin-aldosterone system (RAM) has been a longstanding, butsomewhat ineffective, approach for reducing overactivity of the SNS.

For a more detailed description of pertinent patient anatomy andphysiology, reference may be made to U.S. Patent Application PublicationNo. 2015/0051594, filed Mar. 7, 2013, the entire contents of which areincorporated herein by reference.

The presently disclosed systems, devices, and methods/techniques disruptthe nervous supply to the ovaries in order to control (e.g.,down-regulate) ovarian hormonal secretion and treat hormonally-regulateddiseases such as POCS and PMDD. By disrupting the ovarian nerve supply,hormonal overproduction leading to disease states may be effectivelytreated.

Turning now to FIGS. 4, 5A, and 5B, an ovary denervation system 100, inaccordance with one embodiment of the present disclosure, includes aguide tube 102 secured to a transvaginal ultrasound probe 104, and adisruptor 106 (e.g., an ablation device) that is selectively advanceablerelative to guide tube 102 (e.g., therethrough). Guide tube 102 ispositioned to guide disruptor 106 toward the ovary so that disruptor 106is maintained in alignment with a plane “P” of ultrasound projected fromtransvaginal ultrasound probe 104. Guide tube 102 may have a curveddistal portion 102 a that curves away from transvaginal ultrasound probe104 to guide or otherwise direct disruptor 106 toward the ovary asdisruptor 106 is advanced through guide tube 102. Once disruptor 106 ispositioned adjacent to ovarian anatomy, disruptor 106 can be activatedto disrupt (e.g., ablate) ovarian nerves. For a more detaileddescription of example disruptors, such as microwave ablation devices,reference can be made to U.S. Pat. Nos. 9,247,992, 9,119,650, or U.S.Patent Application Publication No. 2013/0317495, the entire contents ofeach of which are incorporated herein by reference. As used herein, theterm “ablation device” may refer to any device that ablates tissuethrough direct application of heat, cooling, electrosurgical current,ultrasonic vibration, other energy transfer, etc., or combinationsthereof.

As seen in FIG. 5A, a method for ovarian denervation includes insertingdisruptor 106 into the ovaries and/or surrounding tissue through thevagina and vaginal fornix (see, for example, paths “X1” and “X2”illustrating the trans-fornix approach) under direct ultrasoundguidance, for example, from transvaginal ultrasound probe 104 supportedwithin the vagina. Transvaginal ultrasound probe 104 can be positionedwithin the vagina to project ultrasound through vaginal anatomy towardthe ovary to enable visualization and facilitate positioning ofdisruptor 106 relative to ovaries, ovarian nerves, etc. so thatdisruptor 106 can be accurately positioned to disrupt the ovarian nervesupply upon application thereof. This trans-fornix approach may besimilar to the manner in which an oocyte retrieval needle is placed intothe ovary during IVF egg retrieval.

With reference to FIG. 6, according to another aspect of the presentdisclosure, one method for ovarian denervation includes passing adisruptor (e.g., disruptor 106) along a path or trajectory “X3” thatextends through the cervix and into the fallopian tubes so as to definea trans-fallopian approach. The disruptor is advanced to a location “I”where the infundibulopelvic ligament passes across and adjacent to therespective fallopian tube. Once the disruptor is in position at location“I,” the disruptor can be applied to effectuate local treatment, forinstance, by ablating ovarian nerves contained within theinfundibulopelvic ligament. To facilitate visualization, any suitableguidance technique may be utilized to confirm disruption (e.g.,ablation) is occurring at the desired location along the fallopian tube.For example, such guidance techniques may include ultrasound (e.g.,transvaginal ultrasound probe 104 seen in FIG. 4), fluoroscopy, etc., orcombinations thereof.

With continued reference to FIG. 6, in some aspects of the presentdisclosure, one or more of the presently disclosed systems and/ordevices (e.g., the disruptor 106) may be advanced through (e.g., viapiercing, puncturing, etc.) the fundus of the patient's uterus to accessthe infundibulopelvic ligament and/or ovarian nerves thereof, forexample, in addition to, and/or instead of, through the fallopian tubes.

Turning now to FIG. 7, in one aspect of the present disclosure, anothermethod for ovarian denervation includes positioning (temporarily orpermanently implanting) disruptors, such as one or more electrodes 110,112, within (e.g., electrode 110), and/or adjacent to (e.g., electrode112), the ovarian artery for acting on the ovarian nerve supply.Electrodes 110, 112 are configured to be activated to apply electricalstimulus (e.g., electrical energy) to tissues/nerves of theinfundibulopelvic ligament, effectively disrupting the sympathetic nervesignals transmitted through the ovarian nerves. The implanted electrodes110, 112 may be configured to apply electrical stimulus continuously orintermittently. The electrical stimulus may be modulated, depending onthe severity of symptom or phase of the patient's menstrual cycle.Electrodes 110, 112 may be coupled to an energy source such as anelectrosurgical generator “EG” that selectively transmits electricalenergy to electrodes 110, 112. For a more detailed description of oneexample of an electrosurgical generator, reference can be made to U.S.Pat. No. 8,784,410, the entire contents of which are incorporated byreference herein.

With reference to FIG. 8, according to a further aspect of the presentdisclosure, one method for ovarian denervation includes providing anenergy source “ES” outside a patient and positioning the energy source“ES” so as to enable application of focused energy “E” to the ovary, thetissues surrounding the ovary, and/or the ovarian vessel (e.g., artery),in order to disrupt the nerve supply. Any suitable energy applicationtechnique may be utilized and may be applied directly (e.g., such thattarget site is externally exposed) or indirectly (e.g., such that thetarget site is not externally exposed and energy is required to passthrough other tissue first). For example, the energy source “ES” can beconfigured to provide focused ultrasound, focused radiation (e.g.,gamma-knife), focused microwave energy, light, etc., or combinationsthereof. The energy source “ES” may include a cyclotron, a linearaccelerator, a kilovoltage unit, a teletherapy unit, etc., orcombinations thereof.

Referring now to FIG. 9, in yet another aspect of the presentdisclosure, a method for ovarian denervation includes applying a beam ofelectrosurgical plasma “EP,” from a disruptor such as a plasma emitter200 (e.g., an argon plasma emitter), to a surface of theinfundibulopelvic ligament to ablate the sympathetic nerves “N” runningalong the outer surface of the ovarian artery for denervating theovarian nerve supply. For a more detailed description of an example ofplasma emitter, reference can be made to U.S. Pat. No. 6,039,736, theentire contents of which are incorporated herein by reference.

According to another aspect of the present disclosure, one method forovarian denervation includes applying light at a controlled frequency(e.g., photoablation with a laser), with a disruptor such as a lightemitting instrument (not shown), to the tissues of the infundibulopelvicligament (see FIG. 1A, 9) or to the tissue surrounding the ovary toablate ovarian nerve tissue. For example, photoablation with a laser(e.g. an excimer or exiplex laser) having a wavelength of approximately200 nm may be used to disrupt ovarian nerves. With a controlledfrequency of light, more energy can be absorbed by nerve tissue than byother surrounding tissue so that the nerves are locally ablated withminimal surrounding tissue damage.

Turning now to FIG. 10, in still another aspect of the presentdisclosure, one method for ovarian denervation includes applying adisruptor such as a mechanical resection device (e.g., a scalpel) orshaver blade 300 to the surface of the ovarian artery to denervate(e.g., mechanically disrupt and resect) the ovarian nerves at the outersurface of the ovarian artery (e.g., by cutting and/or scraping).

As seen in FIGS. 11A and 11B, in one aspect of the present disclosure,still another method for ovarian denervation includes introducing adisruptor, in the form of a balloon catheter 400, into one or moreovarian vessels within the infundibulopelvic ligament. A balloon 402 ofballoon catheter 400 can be inflated with inflation fluid (e.g., saline)from an inflation source (not shown) coupled to balloon catheter 400. Inparticular, balloon 402 can be selectively inflated within an ovarianvessel to a threshold volume so that the ovarian vessel wall expands anamount sufficient to mechanically tear or disrupt one or more nervesrunning along the ovarian vessel without causing the wall of the ovarianvessel to tear. Balloon 402 may then be deflated so that ballooncatheter 400 can be withdrawn. Although described with respect to aballoon, any suitable expandable structure can be utilized (e.g., astent, radially extendable prongs, etc.). The expandable structure(e.g., balloon 402) may be deflated and/or re-inflated as desired, forexample, to repeat the technique at one or more additional locationsalong the vessel or in another vessel. For a more detailed descriptionof an example of balloon catheter, reference can be made to U.S. PatentApplication Publication No. 2014/0250661, the entire contents of whichare incorporated herein by reference.

As seen in FIGS. 12A-12C, in certain aspects of the present disclosure,the myelin sheath surrounding the ovarian nerves may be disrupted, forexample, with the disruptor 106 (or utilizing any of the other presentlydisclosed devices, systems, and/or techniques), to effectuate ovariandenervation.

Any of the presently disclosed techniques can be effectuatedindividually or in any suitable combination.

The various embodiments/techniques disclosed herein may also beconfigured to work with robotic surgical systems and what is commonlyreferred to as “Telesurgery.” Such systems employ various roboticelements to assist the clinician and allow remote operation (or partialremote operation) of surgical instrumentation. Various robotic arms,gears, cams, pulleys, electric and mechanical motors, etc. may beemployed for this purpose and may be designed with a robotic surgicalsystem to assist the clinician during the course of an operation ortreatment. Such robotic systems may include remotely steerable systems,automatically flexible surgical systems, remotely flexible surgicalsystems, remotely articulating surgical systems, wireless surgicalsystems, modular or selectively configurable remotely operated surgicalsystems, etc.

The robotic surgical systems may be employed with one or more consolesthat are next to the operating theater or located in a remote location.In this instance, one team of clinicians may prep the patient forsurgery and configure the robotic surgical system with one or more ofthe instruments disclosed herein while another clinician (or group ofclinicians) remotely controls the instruments via the robotic surgicalsystem. As can be appreciated, a highly skilled clinician may performmultiple operations in multiple locations without leaving his/her remoteconsole which can be both economically advantageous and a benefit to thepatient or a series of patients.

For a detailed description of exemplary medical work stations and/orcomponents thereof, reference may be made to U.S. Patent ApplicationPublication No. 2012/0116416, and PCT Application Publication No.WO2016/025132, the entire contents of each of which are incorporated byreference herein.

Persons skilled in the art will understand that the structures andmethods specifically described herein and shown in the accompanyingfigures are non-limiting exemplary embodiments, and that thedescription, disclosure, and figures should be construed merely asexemplary of particular embodiments. It is to be understood, therefore,that the present disclosure is not limited to the precise embodimentsdescribed, and that various other changes and modifications may beeffected by one skilled in the art without departing from the scope orspirit of the disclosure. Additionally, the elements and features shownor described in connection with certain embodiments may be combined withthe elements and features of certain other embodiments without departingfrom the scope of the present disclosure, and that such modificationsand variations are also included within the scope of the presentdisclosure. Accordingly, the subject matter of the present disclosure isnot limited by what has been particularly shown and described.

What is claimed is:
 1. A method for effectuating ovarian denervation,the method comprising: advancing a disruptor intravaginally and into afallopian tube to access an ovarian nerve; and activating the disruptorto denervate the ovarian nerve.
 2. The method of claim 1, wherein thedisruptor includes an ablation device, and wherein advancing thedisruptor through the fallopian tube includes advancing the ablationdevice through the fallopian tube.
 3. The method of claim 2, whereinactivating the disruptor includes ablating the ovarian nerve with theablation device.
 4. The method of claim 1, further comprising advancingthe disruptor to a position adjacent to an infundibulopelvic ligament.5. The method of claim 1, further comprising advancing an ultrasoundprobe intravaginally and positioning the ultrasound probe to projectultrasound in alignment with an ovary while the disrupter is activated.6. The method of claim 5, wherein the disrupter is coupled to theultrasound probe, and the disruptor and the ultrasound probe areintroduced intravaginally together.
 7. The method of claim 6, furthercomprising advancing the disruptor relative to the ultrasound probe. 8.The method of claim 7, wherein a guide tube is coupled to the ultrasoundprobe, and wherein advancing the disruptor relative to the ultrasoundprobe includes advancing the disruptor through the guide tube.
 9. Themethod of claim 8, wherein advancing the disruptor through the guidetube includes directing the disruptor away from the ultrasound probe asthe disruptor is advanced relative to the ultrasound probe.
 10. Themethod of claim 9, wherein directing the disruptor away from theultrasound probe includes intravaginally positioning the guide tube suchthat the guide tube directs the disruptor toward the uterus.
 11. Themethod of claim 1, wherein activating the disruptor disrupts a myelinsheath of the ovarian nerve without disrupting a nerve fiber of theovarian nerve.
 12. The method of claim 1, wherein activating thedisruptor includes applying microwave energy to the ovarian nerve. 13.The method of claim 1, wherein activating the disruptor includesapplying electrosurgical plasma to the ovarian nerve.
 14. The method ofclaim 1, wherein activating the disruptor includes applying a blade tothe ovarian nerve.
 15. An ovarian denervation system, comprising: anintravaginal ultrasound probe; a guide tube coupled to the intravaginalultrasound probe; and a disruptor advanceable through the guide tube andrelative to the intravaginal ultrasound probe, the disruptor configuredto advance into a fallopian tube to a position adjacent an ovariannerve, the disruptor configured to denervate the ovarian nerve.
 16. Theovarian denervation system of claim 15, wherein the disruptor includesan end effector that is configured to ablate the ovarian nerve withmicrowave energy.
 17. The ovarian denervation system of claim 15,wherein the disruptor includes an end effector that is configured toemit electrosurgical plasma for disrupting the ovarian nerve.
 18. Theovarian denervation system of claim 15, wherein the disruptor includes ablade that is configured to scrape the ovarian nerve.
 19. The ovariandenervation system of claim 15, wherein the guide tube includes a curveddistal portion configured to direct the disruptor toward the fallopiantube.
 20. The ovarian denervation system of claim 15, wherein thedisruptor is configured to disrupt a myelin sheath of the ovarian nervewithout disrupting a nerve fiber of the ovarian nerve.